Alzheimer's disease is a progressive mental deterioration in a human resulting in loss of memory, confusion and disorientation, as well as, behavioral problems such as anxiety. Alzheimer's disease accounts for the majority of senile dementias and is a leading cause of death in adults (Anderson, R. N., Natl. Vital Stat. Rep. 49.1-87 (2001)). The disclosure of the foregoing is incorporated herein in its entirety by reference. In addition, the entirety of the disclosures of each of the publications cited herein are incorporated herein by reference. Currently-used treatments offer a small symptomatic benefit; no treatments to delay or halt the progression of the disease are as yet available.
The cause and progression of Alzheimer's disease are not well understood. Research indicates that the disease is associated with plaques and tangles in the brain (Tiraboschi P., et al., 2004, Neurology 62 (11): 1984-9). Histologically, the brain of persons afflicted with Alzheimer's disease is characterized by a distortion of the intracellular neurofibrils and the presence of senile plaques composed of granular or filamentous argentophilic masses with an amyloid protein core, largely due to the accumulation of β-amyloid protein (Aβ) in the brain. Aβ accumulation plays a role in the pathogenesis and progression of the disease (Selkoe, D. J., Nature 399: 23-31 (1999)) and is a proteolytic fragment of amyloid precursor protein (APP). APP is cleaved initially by β-secretase (also referred to as memapsin 2) followed by γ-secretase to generate Aβ (Lin, X., et al., Proc. Natl. Acad. Sci. USA 97:1456-1460 (2000); De Stropper, B., et al., Nature 391:387-390 (1998)). Without being bound by theory, it is believed that one approach to the treatment of Alzheimer's disease is to inhibit the production of Aβ.
It has been discovered herein that the compounds described herein are useful for treating Alzheimer's disease. In one embodiment of the invention, compounds are described herein for treating Alzheimer's disease. In another embodiment of the invention, pharmaceutical compositions are described herein for treating Alzheimer's disease where the pharmaceutical compositions include one or more of the compounds described herein in a therapeutically effective amount. In another embodiment of the invention, methods for treating Alzheimer's disease in a patient in need of relief are described herein, where the methods include the step of administering a therapeutically effective amount of one or more compounds and/or one or more pharmaceutical compositions described herein. In another embodiment of the invention, uses of the one or more compounds and/or one or more pharmaceutical compositions described herein in the manufacture of a medicament for treating Alzheimer's disease are described herein. Without being bound by theory, it is believed that the efficacy of the compounds herein described may be due at least in part to their potency in inhibiting the proteolytic activity of the enzyme memapsin 2.
It is to be understood that the compounds described herein may be used alone or in combination with other compounds useful for treating Alzheimer's disease, including those compounds that may operate by the same or different modes of action. It is also to be understood that the compounds described herein may be used in combination with other compounds to improve cognitive properties as well as anxiolytics and antipsychotics to control behavior.